The proposed work seeks to define the relationship of mucosal hyperplasia to large bowel cancer using a model system of benign mucosal proliferation (TMCH) interacting with the chemical carcinogen 1,2-dimethylhydrazine (DMH). TMCH is a disease of mice caused by Citrobracter freundii. It manifests itself by having autoradiographic cytokinetics similar to preneoplastic and neoplastic lesions of the bowel and is influenced by factors such as diet and genetics. Studies underway indicate that TMCH promotes the early phases of DMH carcinogenesis by reducing the latent period for the appearance of DMH atypias and increases the sensitivity of the mucosa to low and single doses of DMH. Sequential studies are being performed to follow the course of early DMH atypias following a single dose of DMH in concert with TMCH. Initial experiments indicated that atypias regress, rather than progress to overt neoplasia. The proposed studies will also examine the significance of mucin histochemical changes, mucosal cytokinetics and lesion morphology considered characteristic for preneoplasia or neoplasia. Several of these characteristics have been shown to also occur in the reversible proliferative lesions of TMCH.